Sjogren-Larsson Syndrome: Mechanisms and Management.

Abstract

Sjogren Larsson syndrome (SLS) is a rare autosomal recessive inborn error of lipid metabolism due to mutations in the ALDH3A2 that result in a deficiency of fatty aldehyde dehydrogenase (FALDH). The syndrome has a high prevalence in Sweden where it was first described, but now known to occur worldwide. The classical triad of ichthyosis, mental retardation and spasticity characterizes clinical features. Preterm birth is common. "Glistening white dots" in the retina is a pathognomic clinical feature. Magnetic resonance imaging of the brain demonstrates leukoencephalopathy predominant in the periventricular region. Cerebral MR spectroscopy reveals a characteristic abnormal lipid peak at 1.3ppm and a small peak at 0.9ppm. The primary role of FALDH is oxidation of medium and long-chain aliphatic aldehydes derived from fatty alcohol, phytanic acid, ether glycerolipids and sphingolipids. The diagnosis is based on the typical phenotype, demonstration of the enzyme deficiency and presence of biallelic mutations in the ALDH3A2. The management of SLS largely remains symptomatic currently. However, several potential therapeutic options are being developed, keeping in view of the fundamental metabolic defects or correcting the genetic defect. This review aims to summarize the clinical, genetic and biochemical findings, pathogenetic mechanisms and the current therapeutic options, in SLS.